OP0164 SAFETY AND EFFICACY OF UPADACITINIB FOR PEDIATRIC PATIENTS WITH POLYARTICULAR COURSE JUVENILE IDIOPATHIC ARTHRITIS: AN INTERIM ANALYSIS OF AN OPEN-LABEL, PHASE 1 TRIAL
Authors: H. Brunner, G. Horneff, I. Foeldvari, J. Anton, M. E. Mohamed, Y. Qian, K. Unnebrink, S. Hao, H. Camp, N. Khan, A. Shmagel
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Novel treatment options are needed for pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Upadacitinib (UPA) is an oral, selective Janus kinase (JAK) inhibitor with a positive benefit-risk profile in adult patients with moderate-to-severe active rheumatoid arthritis.<sup>[1,2]</sup> <h3>Objectives</h3> To evaluate the safety and efficacy of UPA in pediatric patients with pcJIA. <h3>Methods</h3> This open-label, 3-part, phase 1 trial (NCT03725007) enrolled pediatric patients aged 2 to &lt; 18 years with pcJIA and ≥ 5 active joints at 31 sites across North America, Europe, and Asia. UPA was dosed as a twice-daily oral solution or once-daily tablet based on body weight. Part 1 evaluated multiple ascending doses of UPA for 7 days. Parts 2 and 3 evaluated long-term safety and efficacy of UPA for up to 156 weeks. This interim analysis (cutoff date of 22 September 2022) evaluated all available safety data in parts 1, 2, and 3; efficacy was evaluated in parts 1 and 2 through week 12. Efficacy endpoints included the JIA American College of Rheumatology (JIA ACR) 30, 50, and 70 response; the Childhood Health Assessment Questionnaire (C-HAQ); and the 27-point Juvenile Arthritis Disease Activity Score based on C-reactive Protein (JADAS-27 [CRP]). <h3>Results</h3> A total of 57 pediatric patients (78.9% female) with mean (SD) age of 9.5 (4.4) years and mean (SD) weight of 38.1 (20.4) kg received UPA; of these, 51 patients were treated in parts 1 and 2. In part 1, 8 (15.7%) of 51 patients reported adverse events (AEs) through 7 days; no patients reported serious AEs or AEs leading to treatment discontinuation. At a mean (median) duration of exposure of 514.9 (412.0) days, 52 (91.2%) of 57 patients reported AEs that were predominately mild to moderate in severity (<b>Table 1</b>). The most common treatment-emergent AEs were COVID-19 infection (n = 23/57, 40.4%), upper respiratory tract infection (n = 23/57, 40.4%), nasopharyngitis (n = 13/57, 22.8%), gastroenteritis (n = 10/57, 17.5%), pyrexia (n = 10/57, 17.5%), abdominal pain (n = 9/57, 15.8%), and nausea (n = 8/57, 14.0%). The most common AEs of special interest included elevated creatine phosphokinase levels (n = 6/57, 10.5%), hepatic disorder (n = 3/57, 5.3%), and neutropenia (n = 2/57, 3.5%); all were nonserious events. Six (31.6%) of 19 patients in the group aged 12 to &lt;18 years reported serious AEs and 2 (10.5%) reported AEs leading to treatment discontinuation. A high proportion of patients across all age groups achieved JIA ACR30, 50, and 70 response at week 12 (<b>Figure 1</b>). Improvement from baseline to week 12 in C-HAQ and JADAS-27 [CRP] scores was observed across all age groups. <h3>Conclusion</h3> In pediatric patients with pcJIA, UPA was well tolerated and associated with improvements in disease activity and physical function at week 12. <h3>References</h3> [1] Burmester GR, et al. <i>Lancet.</i> 2018;391:2503-12. [2] Smolen JS, et al. <i>Lancet.</i> 2019;393:2303-11. <h3>Acknowledgements</h3> AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approving the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. All authors agreed to submit this abstract to the EULAR 2023 Congress. Medical writing support was provided by Michael Dyle, PhD, of JB Ashtin, and funded by AbbVie. <h3>Disclosure of Interests</h3> Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, and Pfizer, Consultant of: AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cerocor, Eli Lilly, EMD Serono, Idorsia, Janssen, GlaxoSmithKline, F Hoffmann-La Roche, Merck, Novartis, R-Pharm, and Sanofi, Gerd Horneff Grant/research support from: AbbVie, Bayer, Chugai, GlaxoSmithKline, MSD, Novartis, Pfizer, Roche, Sanofi, and Sobi, Ivan Foeldvari Consultant of: Eli Lilly, Hexal, Medac, Novartis, and Pfizer, Jordi Anton Consultant of: AbbVie, Alexion, Amgen, Gebro, GSK Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, and Lilly, Grant/research support from: AbbVie, Alexion, Amgen, Gebro, GSK Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, and Lilly, Mohamed-Eslam Mohamed Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Yuli Qian Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Kristina Unnebrink Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Shuai Hao Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Heidi Camp Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Nasser Khan Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie, Anna Shmagel Shareholder of: May hold AbbVie stock or stock options, Employee of: AbbVie.